RCSD1

Summary

RCSD1 (RCSD domain containing 1, HGNC:28310) is a protein-coding gene on chromosome 1q24.2, encoding CapZ-interacting protein (Q6JBY9). Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly.

Enables actin filament binding activity. Involved in cellular hyperosmotic response. Predicted to be located in actin filament. Predicted to be part of WASH complex. Predicted to be active in early endosome.

Source: NCBI Gene 92241 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 78 total
• Druggable target: yes
• MANE Select transcript: NM_052862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28310
Approved symbol	RCSD1
Name	RCSD domain containing 1
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MK2S4, MGC21854, CapZIP
Ensembl gene	ENSG00000198771
Ensembl biotype	protein_coding
OMIM	610579
Entrez	92241

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000361496, ENST00000367854, ENST00000461790, ENST00000472038, ENST00000475127, ENST00000537350, ENST00000900257, ENST00000900258, ENST00000900259, ENST00000900260, ENST00000900261, ENST00000958982

RefSeq mRNA: 3 — MANE Select: NM_052862 NM_001322923, NM_001322924, NM_052862

CCDS: CCDS1263, CCDS81396

Canonical transcript exons

ENST00000367854 — 7 exons

Exon	Start	End
ENSE00000958443	167683900	167684001
ENSE00000958444	167685421	167685510
ENSE00000958445	167690049	167690120
ENSE00000958446	167694099	167694302
ENSE00001215560	167704664	167708696
ENSE00001510815	167697099	167697842
ENSE00003843126	167630232	167630429

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 97.64.

FANTOM5 (CAGE): breadth broad, TPM avg 23.1508 / max 966.8626, expressed in 826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6450	12.4796	734
6449	5.2450	644
6451	5.0633	600
6448	0.3007	166
6454	0.0622	21

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	97.64	gold quality
monocyte	CL:0000576	97.62	gold quality
granulocyte	CL:0000094	97.07	gold quality
thymus	UBERON:0002370	96.50	gold quality
vastus lateralis	UBERON:0001379	96.07	gold quality
lymph node	UBERON:0000029	95.99	gold quality
quadriceps femoris	UBERON:0001377	95.99	gold quality
bone marrow	UBERON:0002371	95.91	gold quality
blood	UBERON:0000178	95.48	gold quality
biceps brachii	UBERON:0001507	94.60	gold quality
bone marrow cell	CL:0002092	94.56	gold quality
vermiform appendix	UBERON:0001154	94.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.34	gold quality
skeletal muscle tissue	UBERON:0001134	94.29	gold quality
left ventricle myocardium	UBERON:0006566	94.00	gold quality
spleen	UBERON:0002106	93.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.58	gold quality
deltoid	UBERON:0001476	93.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.00	gold quality
muscle tissue	UBERON:0002385	92.93	gold quality
trabecular bone tissue	UBERON:0002483	92.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.51	gold quality
caecum	UBERON:0001153	91.86	gold quality
tibialis anterior	UBERON:0001385	91.39	gold quality
ileal mucosa	UBERON:0000331	91.27	gold quality
myocardium	UBERON:0002349	90.54	gold quality
muscle of leg	UBERON:0001383	89.67	gold quality
gastrocnemius	UBERON:0001388	88.95	gold quality
epithelium of nasopharynx	UBERON:0001951	87.95	gold quality
heart right ventricle	UBERON:0002080	87.18	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	2374.31
E-MTAB-9906	yes	851.00
E-HCAD-4	yes	87.05
E-HCAD-6	yes	62.16
E-CURD-88	yes	45.11
E-CURD-112	yes	44.58
E-ENAD-20	yes	44.58
E-HCAD-10	yes	24.67
E-ANND-3	yes	18.29
E-MTAB-9067	yes	18.18
E-MTAB-9801	yes	6.16
E-CURD-119	yes	4.48
E-MTAB-10042	yes	4.45
E-MTAB-7606	no	676.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting RCSD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-5001-3P	98.91	67.28	1394

Literature-anchored findings (GeneRIF, showing 2)

• The structure and function of CapZ-interacting protein are reported. (PMID:15850461)
• CapZIP is fused to ABL1 in a t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia (PMID:17541395)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dub	ENSDARG00000059774
danio_rerio	zgc:153184	ENSDARG00000099645
mus_musculus	Rcsd1	ENSMUSG00000040723
rattus_norvegicus	Rcsd1	ENSRNOG00000003283
drosophila_melanogaster	FAM21	FBGN0034529

Paralogs (2): WASHC2A (ENSG00000099290), WASHC2C (ENSG00000172661)

Protein

Protein identifiers

CapZ-interacting protein — Q6JBY9 (reviewed: Q6JBY9)

Alternative names: Protein kinase substrate CapZIP, RCSD domain-containing protein 1

All UniProt accessions (3): Q6JBY9, B7ZKW8, F6T4W9

UniProt curated annotations — full annotation on UniProt →

Function. Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly.

Subunit / interactions. Interacts with CAPZA2 and CAPZB.

Tissue specificity. Highly expressed in skeletal muscle and more weakly in cardiac muscle. Also expressed in several lymphoid organs, including spleen, thymus, peripheral blood leukocytes, lymph node and bone marrow.

Post-translational modifications. Dephosphorylation results in its dissociation from CAPZA2.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6JBY9-1	1	yes
Q6JBY9-2	2

RefSeq proteins (3): NP_001309852, NP_001309853, NP_443094* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007850	RCSD	Domain
IPR029341	FAM21/CAPZIP	Domain

Pfam: PF05177, PF15255

UniProt features (40 total): modified residue 25, compositionally biased region 6, sequence conflict 3, region of interest 2, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6JBY9-F1	56.03	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (25): 17, 68, 82, 83, 105, 108, 116, 120, 123, 124, 126, 127, 135, 143, 177, 179, 216, 244, 267, 268 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): BENPORATH_ES_WITH_H3K27ME3, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_HYPEROSMOTIC_RESPONSE, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, GOBP_MUSCLE_CONTRACTION, MODULE_301, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, BERTUCCI_INVASIVE_CARCINOMA_DUCTAL_VS_LOBULAR_DN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, MARSON_FOXP3_TARGETS_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_ACTIN_BINDING

GO Biological Process (4): skeletal muscle contraction (GO:0003009), protein localization to endosome (GO:0036010), retrograde transport, endosome to Golgi (GO:0042147), cellular hyperosmotic response (GO:0071474)

GO Molecular Function (3): actin filament binding (GO:0051015), phosphatidylinositol phosphate binding (GO:1901981), retromer complex binding (GO:1905394)

GO Cellular Component (4): early endosome (GO:0005769), cytosol (GO:0005829), actin filament (GO:0005884), WASH complex (GO:0071203)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-containing complex binding	2
cytoplasm	2
striated muscle contraction	1
musculoskeletal movement	1
protein localization to organelle	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
hyperosmotic response	1
cellular response to osmotic stress	1
actin binding	1
phospholipid binding	1
endosome	1
cellular anatomical structure	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
protein-containing complex	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCSD1	CAPZA1	P52907	868
RCSD1	MAPKAPK2	P49137	692
RCSD1	MAPKAPK3	Q16644	691
RCSD1	MAPK12	P53778	656
RCSD1	MAPK13	O15264	648
RCSD1	NUP214	P35658	625
RCSD1	ABL1	P00519	589
RCSD1	CARMIL1	Q5VZK9	523
RCSD1	ABL2	P42684	507
RCSD1	ZMIZ1	Q9ULJ6	477
RCSD1	EML1	O00423	447
RCSD1	TMC8	Q8IU68	406
RCSD1	SNX2	P82862	399
RCSD1	PLEKHO1	Q53GL0	395
RCSD1	SASH3	O75995	394

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RCSD1	CAPZA2	psi-mi:“MI:0914”(association)	0.530
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
NSUN2	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
RCSD1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): RCSD1 (Biochemical Activity), RCSD1 (Biochemical Activity), RCSD1 (Biochemical Activity), CAPZA1 (Affinity Capture-Western), CAPZA2 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), RCSD1 (Proximity Label-MS), RCSD1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), COLGALT1 (Co-fractionation), RCSD1 (Affinity Capture-MS), RCSD1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I5ZM56, A2AJI0, A2AKB4, D3ZFB6, E9PUL5, O08715, O75128, O88884, P18302, Q07266, Q0VGB7, Q149B8, Q2KI80, Q32LQ1, Q3UZ39, Q3UZA1, Q498S6, Q4V9L6, Q5FVJ4, Q5RAC1, Q5T7N3, Q60829, Q66HF9, Q6J4I0, Q6JBY9, Q6NV74, Q6P9J5, Q6PG95, Q6PJW8, Q6ZNL6, Q6ZSG2, Q7Z6L0, Q80XI1, Q8BGW2, Q8BRJ3, Q8CBC4, Q8CCJ4, Q8IY92, Q8K124, Q8NC24

Diamond homologs: Q3UZA1, Q3ZBT0, Q5RDC1, Q641Q2, Q6JBY9, Q6PGL7, Q80X08, Q91Y25, Q9Y4E1, Q552E2

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MAPKAPK2	“down-regulates activity”	RCSD1	phosphorylation
MAPKAPK3	“down-regulates activity”	RCSD1	phosphorylation
MAPK12	“down-regulates activity”	RCSD1	phosphorylation
MAPK13	“down-regulates activity”	RCSD1	phosphorylation
MAPK8	“down-regulates activity”	RCSD1	phosphorylation
RCSD1	up-regulates	CAPZA1	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1410 predictions. Top by Δscore:

Variant	Effect	Δscore
1:167683891:A:AG	acceptor_gain	1.0000
1:167683891:ATTT:A	acceptor_gain	1.0000
1:167683892:T:G	acceptor_gain	1.0000
1:167683894:T:A	acceptor_gain	1.0000
1:167683895:GCCA:G	acceptor_loss	1.0000
1:167683897:CA:C	acceptor_loss	1.0000
1:167683898:A:AG	acceptor_gain	1.0000
1:167683898:AG:A	acceptor_gain	1.0000
1:167683899:G:GC	acceptor_gain	1.0000
1:167683899:GG:G	acceptor_gain	1.0000
1:167683899:GGA:G	acceptor_gain	1.0000
1:167683899:GGAA:G	acceptor_gain	1.0000
1:167683899:GGAAA:G	acceptor_gain	1.0000
1:167683998:GGAG:G	donor_gain	1.0000
1:167683999:G:GT	donor_gain	1.0000
1:167683999:GAG:G	donor_gain	1.0000
1:167684001:GGT:G	donor_loss	1.0000
1:167684002:G:GC	donor_loss	1.0000
1:167694462:A:AG	acceptor_gain	1.0000
1:167694462:AAAT:A	acceptor_gain	1.0000
1:167694463:A:G	acceptor_gain	1.0000
1:167630427:G:GT	donor_gain	0.9900
1:167630428:AGGTA:A	donor_loss	0.9900
1:167630429:GGTAA:G	donor_loss	0.9900
1:167630430:GTAAA:G	donor_loss	0.9900
1:167684002:G:GG	donor_gain	0.9900
1:167684003:T:A	donor_loss	0.9900
1:167690047:A:AG	acceptor_gain	0.9900
1:167690048:G:GG	acceptor_gain	0.9900
1:167690048:GA:G	acceptor_gain	0.9900

AlphaMissense

2696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:167697125:G:C	R167S	0.998
1:167697125:G:T	R167S	0.998
1:167697124:G:T	R167M	0.997
1:167697126:C:A	R168S	0.997
1:167697139:G:T	R172M	0.997
1:167690107:T:A	I86N	0.996
1:167697122:A:C	K166N	0.996
1:167697122:A:T	K166N	0.996
1:167697124:G:C	R167T	0.996
1:167697140:G:C	R172S	0.996
1:167697140:G:T	R172S	0.996
1:167690116:T:C	L89P	0.995
1:167697139:G:C	R172T	0.995
1:167690116:T:A	L89H	0.994
1:167694099:G:C	A91P	0.994
1:167697120:A:G	K166E	0.994
1:167694150:A:C	S108R	0.991
1:167694152:T:A	S108R	0.991
1:167694152:T:G	S108R	0.991
1:167697136:C:T	S171F	0.991
1:167690110:A:T	E87V	0.990
1:167694106:T:C	L93S	0.990
1:167694258:T:C	F144L	0.990
1:167694260:C:A	F144L	0.990
1:167694260:C:G	F144L	0.990
1:167683973:T:C	F27S	0.989
1:167690107:T:G	I86S	0.989
1:167690120:G:C	Q90H	0.989
1:167690120:G:T	Q90H	0.989
1:167697126:C:G	R168G	0.989

dbSNP variants (sampled 300 via entrez): RS1000000830 (1:167657664 T>C), RS1000031873 (1:167657303 G>C), RS1000034004 (1:167668951 A>G), RS1000049277 (1:167693646 G>A,C), RS1000104543 (1:167702048 C>G), RS1000125171 (1:167698506 G>A,T), RS1000170497 (1:167683397 T>C), RS1000187791 (1:167671202 C>T), RS1000190620 (1:167663016 A>G), RS1000198322 (1:167639792 C>G,T), RS1000202902 (1:167698763 A>G), RS1000274222 (1:167677645 TAGAGG>T), RS1000310352 (1:167705127 T>C), RS1000317566 (1:167668221 G>T), RS1000325128 (1:167667198 G>A)

Disease associations

OMIM: gene MIM:610579 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009798_40	Asthma	8.000000e-11
GCST90002398_501	Neutrophil count	5.000000e-17
GCST90002407_13	White blood cell count	1.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067241 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.31	Kd	48.88	nM	CHEMBL5653589
7.29	ED50	51.55	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149212: Binding affinity to human RCSD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0489	uM

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652254	Binding	Binding affinity to human RCSD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.